Ren-Jie Zhang

This study compared Hounsfield unit (HU) measurements obtained from different regions of interest (ROIs) on lumbar CT for assessing bone mineral density (BMD) and discriminating osteoporosis and thoracolumbar fragility fracture status, aiming to evaluate whether ROI selection meaningfully influences HU-based assessment. Five HU measurement methods were evaluated using lumbar CT. Their correlations with dual-energy X-ray absorptiometry (DEXA)-derived BMD and their discriminative performance for osteoporosis and thoracolumbar fragility fracture status were analyzed. Receiver operating characteristic (ROC) curves were constructed, and pairwise comparisons of areas under the curve (AUCs) were performed using the DeLong test. A sensitivity analysis was additionally conducted after excluding substituted vertebral levels and recalculating mean lumbar HU using only non-substituted vertebrae. All five HU measurement methods showed significant correlations with DEXA-derived BMD, and no statistically significant differences in discriminative performance were observed among the five ROI methods in the primary analysis. In the sensitivity analysis excluding substituted vertebral levels, the AUCs remained comparable across methods for osteoporosis (0.816-0.826) and thoracolumbar fragility fracture status (0.677-0.689), with all pairwise DeLong tests showing no statistically significant differences (all p > 0.05). Different lumbar CT ROI methods demonstrated comparable performance in assessing BMD and discriminating thoracolumbar fragility fracture status, and sensitivity analysis confirmed that exclusion of substituted vertebral levels did not materially affect the results. No ROI method showed statistically significant superiority, suggesting that ROI selection may be guided by clinical feasibility and workflow convenience rather than by diagnostic performance alone. This study compares five commonly used lumbar CT HU measurement methods and shows that their performance is broadly similar. The findings suggest that ROI selection may be guided primarily by clinical feasibility and workflow convenience, although further external validation is required before routine clinical application.

Background Intervertebral disc (IVD) degeneration (IDD) is a leading cause of low back pain, with limited treatment options. The degenerative disc’s harsh microenvironment promotes nucleus pulposus-derived mesenchymal stem cells (NP-MSCs) death and hinders self repair. Mesencephalic astrocyte-derived neurotrophic factor (MANF), an atypical neurotrophic factor, has protective effects in degenerative diseases. However, its role in IDD is unclear. Methods Assessment of MANF expression was conducted in both human nucleus pulposus tissues and a rat IVD puncture model. An in vitro model of degeneration was established by acid treatment of NP-MSCs, and the functional role of MANF was explored through its knockdown and overexpression. RNA sequencing was employed to identify downstream targets. The therapeutic potential of MANF-overexpressing NP-MSCs was evaluated in a rat puncture model. Results MANF expression was markedly downregulated in degenerated IVD tissues from both human patients and rat models. Correspondingly, in vitro experiments demonstrated that MANF knockdown exacerbated, while its overexpression mitigated, acid-induced apoptosis of NP-MSCs. Mechanistically, MANF attenuated mitochondrial dysfunction and ER stress of NP-MSCs under acidic conditions by maintaining MAM integrity, as demonstrated by the complete abolition of this protection upon treatment with the MAM uncoupler FATE1. Transcriptomic analysis and subsequent validation identified receptor expression-enhancing protein 1 (REEP1) as a critical downstream effector through which MANF safeguards MAM integrity. We further elucidated that MANF upregulates REEP1 expression by directly inhibiting miR-33b-5p. In vivo, transplantation of MANF-overexpressing NP-MSCs effectively attenuated IDD in a rat model. Conclusion MANF protected NP-MSCs from acidosis by sustaining MAM integrity via the MiR-33b-5p/REEP1 axis. These findings reveal MANF’s mechanism and therapeutic potential for IDD.

Objective: To identify practical vertebral HU measurement strategies for opportunistic bone mineral density (BMD) screening using routine CT. Methods: Seven anatomical segmental combinations were defined: upper thoracic (T1–T4, UT), mid-thoracic (T5–T8, MT), lower thoracic (T9–T12, LT), thoracolumbar (T11–L2, TL), upper lumbar (L1–L2, UL), lower lumbar (L3–L5, LL), and sacral (S1–S2, SA). Correlations between HU and DEXA-derived T-score were analyzed for both single vertebrae and multi-segment combinations, using the full-segment average (T1–S2, TS) as reference. Stepwise linear regression across 19 vertebrae generated an exploratory combination (EC) model. ROC analysis and age–sex subgroup analyses were performed. Results: A total of 300 patients were enrolled (150 males, 150 females; mean age 54.94 ± 14.39 years). Both single- and multi-segment measurements correlated positively with T-score. TS showed the strongest correlation ( r = 0.799) and highest predictive performance (AUC = 0.914). Among single vertebrae, T5 showed the strongest correlation ( r = 0.785). Among anatomical combinations, TL showed one of the strongest correlations ( r = 0.787) and favorable predictive performance (AUC = 0.912). Subgroup analyses showed stable TL performance across sex groups, whereas the strongest correlation and predictive performance were observed in the 51–60-year age subgroup. Conclusion: Both single- and multi-segment HU measurements were effective for BMD assessment. The TL segment represents a practical HU-based assessment approach for opportunistic osteoporosis screening on routine CT, with stable predictive performance and practical clinical value.

Acid-sensing ion channel 1a (ASIC1a) functions as an extracellular acid sensor, with its activation frequently associated with age-related diseases. We aim to investigate the expression pattern of ASIC1a in the ferroptosis of degenerated nucleus pulposus (NP) tissues and NP cells (NPCs), and explore whether ASIC1a-mediated calcium influx regulates ferroptosis in NPCs through the calcium/calmodulin pathway during intervertebral disc degeneration (IVDD). We use NP tissues, NPCs, and Transcriptome sequencing to investigate the effects and mechanism of ASIC1a in ferroptosis during the progression of IVDD. Elevated expression of ASIC1a was associated with the progression of ferroptosis in human degenerated NP tissues. Meanwhile, the expression of ASIC1a remarkably increased as acid-induced ferroptosis progressed in human NPCs. Besides, transcriptomic analysis identified that inhibition of ASIC1a attenuates ECM degradation and ferroptosis. We then confirmed the overexpression of ASIC1a promoted the progression of ferroptosis and ECM degradation in human NPCs in vitro. Moreover, the ferroptosis of NPCs induced by ASIC1a overexpression was ameliorated by the treatment of BAPTA-AM (the intracellular calcium chelator) or calmidazolium (the calmodulin antagonist). ASIC1a mediated acid-induced ferroptosis via calcium/calmodulin signaling in human NPCs. The in vivo study further indicated that the inhibition of ASIC1a activation ameliorated the IVDD by suppressing ferroptosis in the rat model. This study demonstrated that ASIC1a increased as ferroptosis progressed in human NP tissues and human NPCs. The acid-induced ASIC1a upregulation caused increased calcium levels and contributed to the ferroptosis in NPCs partially mediated by calcium/calmodulin signaling.

Objective This study compared single-segment and multi-segment lumbar vertebral bone quality (VBQ) score measurements in assessing bone mineral density (BMD), diagnosing osteoporosis, and predicting thoracolumbar fragility fractures to determine the more accurate and practical method. Methods A retrospective analysis was conducted on patients who underwent lumbar spine MRI and dual-energy X-ray absorptiometry (DEXA) at the First Affiliated Hospital of Anhui Medical University between August 2019 and August 2023. After applying inclusion and exclusion criteria, 210 patients were enrolled(86 with fractures, 124 without). On sagittal T1-weighted MRI images, regions of interest (ROI) were placed within the trabecular bone from L1 to S1 and adjacent cerebrospinal fluid (CSF). VBQ was calculated as the ratio of vertebral trabecular bone signal intensity (SI) to CSF SI. Both single-segment (VBQ_L1, VBQ_L2, VBQ_L3, VBQ_L4, VBQ_L5, VBQ_S1) and multi-segment (VBQ_L1~L4, VBQ_L1~L5, VBQ_L1~S1) VBQ scores were evaluated. Correlations between VBQ and DEXA-derived BMD (BMD_DEXA/T-score) were analyzed. Diagnostic accuracy for osteoporosis and fragility fractures was assessed using receiver operating characteristic (ROC) curves. Results All VBQ scores significantly correlated with BMD_DEXA/T-score. Among single segments, VBQ_L2 showed the strongest correlation with T-score (r = −0.345) and best AUC for osteoporosis and low BMD prediction. Among multi-segment scores, VBQ_L1~L4 had the strongest correlation (r = −0.319) and best overall diagnostic performance (low BMD AUC = 0.696; fracture AUC = 0.580). Conclusion VBQ scores demonstrated weak-to-moderate correlations with BMD_DEXA and limited diagnostic utility (all AUC < 0.70). Among single segments, L2 performed slightly better, whereas the L1 ~ L4 average was marginally superior among multi-segment approaches. VBQ should therefore serve as a supplementary screening adjunct to DEXA or CT, rather than a stand-alone diagnostic tool, especially for patients who have undergone lumbar MRI but cannot access DEXA/CT.

Intervertebral disc (IVD) degeneration (IDD) is a leading cause of lower back pain, and the application of nucleus pulposus–derived stem cells (NPSCs) holds promise for regenerative treatment. However, the harsh microenvironment of degenerative IVDs increases apoptosis in endogenous and transplanted NPSCs, limiting the effectiveness of NPSC‐based therapies. Mitochondria‐associated ER membrane (MAM) facilitates communication between mitochondria and ER and is critical for cellular homeostasis. PACS‐2 is a central regulator of MAM homeostasis. It is found that MAM structure is disrupted in degenerative human and rat IVDs and in NPSCs exposed to an acidic environment, coinciding with reduced PACS‐2 expression and increased apoptosis. In addition, Pacs‐2 knockout mice with IDD displayed accelerated degeneration, accompanied by the exacerbation of ER stress, mitochondrial dysfunction, and apoptosis. Mechanistically, PACS‐2 suppresses phosphorylation and nuclear translocation of the transcription factor SP1, thereby downregulating its downstream target LRRK2. This reduces LRRK2‐mediated ubiquitination and degradation of Mfn2 through the JNK pathway, preserving MAM integrity and promoting NPSC survival. In vivo, transplantation of Pacs‐2–overexpressing NPSCs improved cell survival and enhanced IVD repair in a degenerative model. These findings demonstrate that PACS‐2 supports NPSC‐mediated IVD regeneration by maintaining MAM integrity via the SP1/LRRK2/Mfn2 axis, offering potential therapeutic targets for IDD.

Objective The integration of 5G and robotics technology has been initially introduced in orthopedic surgeries. Research on 5G remote robot-assisted (RA) spinal surgery remains limited, with the existing literature notably lacking comparative analyses of outcomes between 5G remote and conventional robotic procedures. Herein, this study aims to investigate the clinical feasibility and safety of 5G remote RA percutaneous pedicle screw fixation, and compare the clinical and radiographic outcomes between 5G remote and conventional RA pedicle screw placement in single thoracolumbar fracture surgery. Methods A total of 61 consecutive patients with single thoracolumbar fracture who undergoing pedicle screw placement using 5G remote (26 patients) and conventional (35 patients) RA techniques with a 1:1.3 ratio were retrospectively included. Matching was based on age, gender, and body mass index (BMI) to ensure comparability between the two groups. The clinical outcomes were mainly comprised of VAS and ODI scores, surgical time, and intraoperative blood loss; the radiographic outcomes included the preoperative and postoperative anterior vertebral height (AVH), middle vertebral height (MVH), posterior vertebral height (PVH), accuracy of pedicle screw placement assessed using Gertzbein–Robbins scale, and cranial facet joint violation (FJV) assessed using Babu scale. Results When compared to conventional RA techniques, the 5G remote RA techniques demonstrated comparable clinical outcomes in terms of postoperative VAS score, ODI scores, surgical durations, and intraoperative blood loss. Regarding the radiographic outcomes, the 5G remote RA techniques exhibited similar postoperative results to conventional RA techniques, including AVH, MVH, PVH, improvement ratios for AVH, MVH, and PVH compression. Moreover, the rates of optimal pedicle screw placement accuracy were 77.6% in the 5G remote group and 76.9% in the conventional group, indicating no significant difference. Similarly, the rates of cranial FJV in 5G remote and conventional RA groups were 19.0% and 18.3%, respectively, revealing no statistically significant difference. Conclusions The 5G remote RA techniques demonstrated comparable clinical and radiographic outcomes to conventional RA techniques, including relief from back pain (VAS scores), restoration of functional status (ODI scores), maintenance of vertebral height in the injured vertebra, accuracy of pedicle screw placement, and the incidence rate of cranial FJV. The integration of 5G and robotics technology is safe and feasible, yielding promising clinical and radiographic outcomes in thoracolumbar screw fixation surgery.

The death of human nucleus pulposus derived stem cells (NPSCs) is a key factor affecting the endogenous repair capability and degeneration of intervertebral discs (IVD). ASIC1a is thought to be closely associated with cells destiny in IVD degeneration (IVDD). However, its physiological and pathological roles in human NPSCs are unclear. In this study, we found that the content of ASIC1a increased with IVDD in both rats and human discs. In acidosis-treated NPSCs, the expression level of ASIC1a increased, accompanied by inhibition of cells viability and activation of mitochondrial apoptotic pathway. Additionally, ASIC1a overexpression activated the mitochondrial apoptotic pathway and increased the level of cellular and mitochondrial ROS in human NPSCs. Moreover, we demonstrated that the dysfunction of SIRT3-regulated mitochondrial redox homeostasis was involved in ASIC1a overexpression-induced apoptosis in human NPSCs. The in vivo experiments also demonstrated that the ASIC1a/SIRT3 pathway was involved in IVDD. Overall, these findings showed that ASIC1a disrupted mitochondrial function and aggravated mitochondrial oxidative stress by inhibiting the expression of SIRT3, which activated human NPSC apoptosis and aggravated IVDD. These findings provide new insights for the development of innovative treatment strategies for IVDD.HighlightsAcidosis inhibited human NPSCs activity and promoted apoptosis via mitochondria.ASIC1a promoted acidosis-induced apoptosis of human NPSCs.ASIC1a inhibited SIRT3 expression, aggravating mitochondrial oxidative stress.ASIC1a promoted IVDD via mitochondrial oxidative stress and apoptosis.